Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-22 have an effective filing date of 23APR2020.
Status of Claims
Claims 1-22 are currently pending and presented for examination on the merits.
Claims 1, 9, 17, and 19-21 are amended.
Objections Withdrawn
The objection for claim 1 is withdrawn in view of Applicant’s amendments.
Objections Maintained
The objection filed for claim 18, for depending from a rejected claim, is maintained.
Rejections Withdrawn
The rejection filed under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendments.
The rejection filed under Double Patenting has been withdrawn in view of Applicant amendments to claims.
Rejections Maintained
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. In the instant case the claims are drawn to a natural phenomenon, specifically, the relationship between NID1 levels and a diagnosis of hepatocellular carcinoma (HCC). Furthermore the claims do not integrate said judicial exception in to practical application, and the claims do not recite additional elements that amount to significantly more than said judicial exception.
The 2019 Patent Subject Matter Eligibility Guidance (“Guidance”) provides a means of determining whether a particular claim is patent eligible under 35 U.S.C. 101. The Guidance requires an analysis of multiple steps, Steps 1, 2A, and 2B:
Step 1 - Following a determination of the broadest reasonable interpretation of a claim, is the claim drawn to a process, machine, manufacture, or composition of matter? If the answer to this inquiry is “Yes,” the analysis moves on to step 2A.
Step 2A - A two-prong analysis. For prong one, does the claim recite an abstract idea, law of nature, or natural phenomenon? If “Yes,” the analysis proceeds to prong two, which asks whether the claim recites additional elements that integrate the judicial exception into a practical application. If “No,” the analysis moves on to step 2B.
Step 2B - Does the claim recite additional elements that amount to significantly more than the judicial exception? If “No,” the claim is not eligible subject matter under 35 U.S.C. 101.
With respect to Step 1, the claims are drawn to a process, so the answer to Step 1 is “Yes.”
With respect to prong one of Step 2A, the answer is “Yes,” because the claims are drawn to a natural phenomenon, specifically, the relationship between NID1 levels and a diagnosis of HCC.
With respect to prong two of Step 2A, the claims do not recite additional elements that integrate the judicial exception into a practical application. In addition to the recited judicial exception, the claims recite obtaining a sample from the subject, centrifuging the sample to obtain serum, isolating and lysing extracellular vesicles, contacting the sample with a biomarker composition, measuring and comparing a level of the NID1 with a control, and diagnosing the subject having HCC if the level of the NID1 is higher than the control; however these steps primarily relate to routine laboratory practices involving detecting protein expression. As such these steps do not integrate the judicial exception into a practical application. The claims also do not recite any additional method steps that would integrate the recited judicial exception, for example, by applying or using said judicial exception as an indicator to determine whether a particular treatment or prophylaxis for a disease or medical condition should be administered. It is further noted that the claims include an “comparing” and “diagnosing” step, see claim 1, and these steps are abstract ideas, which involves steps that may be carried out by the human mind. Therefore the answer to prong two of the Step 2A analysis is “No.”.
With respect to Step 2B, as indicated above, the claims recite steps related to routine laboratory practices involving detecting protein expression; however these steps were well-understood, routine, and conventional data gathering steps that were practiced by investigators prior to Applicant’s invention. These steps, alone or in combination, fail to qualify as to additional elements that amount to significantly more than the recited judicial exception. Accordingly the answer to the Step 2B analysis is “No,” and therefore the claims are not eligible subject matter under 35 U.S.C. 101.
Claim 2 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. In the instant case the claim is drawn to a natural phenomenon, specifically, the relationship between TNFR1 and AFP levels and a diagnosis of hepatocellular carcinoma (HCC). Furthermore the claim does not integrate said judicial exception into practical application, and the claims do not recite additional elements that amount to significantly more than said judicial exception.
The 2019 Patent Subject Matter Eligibility Guidance (“Guidance”) provides a means of determining whether a particular claim is patent eligible under 35 U.S.C. 101. The Guidance requires an analysis of multiple steps, Steps 1, 2A, and 2B:
Step 1 - Following a determination of the broadest reasonable interpretation of a claim, is the claim drawn to a process, machine, manufacture, or composition of matter? If the answer to this inquiry is “Yes,” the analysis moves on to step 2A.
Step 2A - A two-prong analysis. For prong one, does the claim recite an abstract idea, law of nature, or natural phenomenon? If “Yes,” the analysis proceeds to prong two, which asks whether the claim recites additional elements that integrate the judicial exception into a practical application. If “No,” the analysis moves on to step 2B.
Step 2B - Does the claim recite additional elements that amount to significantly more than the judicial exception? If “No,” the claim is not eligible subject matter under 35 U.S.C. 101.
With respect to Step 1, the claims are drawn to a process, so the answer to Step 1 is “Yes.”
With respect to prong one of Step 2A, the answer is “Yes,” because the claim is drawn to a natural phenomenon, specifically, the relationship between TNFR1 and AFP levels and a diagnosis of HCC.
With respect to prong two of Step 2A, the claims do not recite additional elements that integrate the judicial exception into a practical application. In addition to the recited judicial exception, the claims recite obtaining a sample from the subject, centrifuging the sample to obtain serum, isolating and lysing extracellular vesicles, contacting the sample with a biomarker composition, measuring and comparing a level of the TNFR1 and AFP with a control, and diagnosing the subject having HCC if the level of the TNFR1 and AFP is higher than the control; however these steps primarily relate to routine laboratory practices involving detecting protein expression. As such these steps do not integrate the judicial exception into a practical application. The claims also do not recite any additional method steps that would integrate the recited judicial exception, for example, by applying or using said judicial exception as an indicator to determine whether a particular treatment or prophylaxis for a disease or medical condition should be administered. It is further noted that the claims include an “comparing” and “diagnosing” step, see claim 1, and this step is an abstract idea, which involves steps that may be carried out by the human mind. Therefore the answer to prong two of the Step 2A analysis is “No.”.
With respect to Step 2B, as indicated above, the claims recite steps related to routine laboratory practices involving detecting protein expression; however these steps were well-understood, routine, and conventional data gathering steps that were practiced by investigators prior to Applicant’s invention. These steps, alone or in combination, fail to qualify as to additional elements that amount to significantly more than the recited judicial exception. Accordingly the answer to the Step 2B analysis is “No,” and therefore the claim is not eligible subject matter under 35 U.S.C. 101.
Applicant’s Arguments:
Applicant respectfully traverses.
Specifically, the Office characterizes claim 1 as a correlation between NID 1 levels and HCC. However, claim 1 goes well beyond a mere observation of a natural phenomenon, as the claim recites a multistep method that includes: isolating extracellular vesicles from a serum obtained from the sample; lysing those extracellular vesicles; measuring the amount of the NID1 in the lysed mixed using a defined immunoassay (ELISA); and the method uses a defined monoclonal antibody structure. The dependent claims further include application of quantitative thresholds, for example. (see, e.g., claims 7 and 8).
Applicant respectfully submits that the Office improperly characterizes the claim by isolating the 'comparing' and 'diagnosing' steps, but ignoring the claim as a whole, which requires specific, physical steps that cannot be characterized as a natural phenomenon or mental steps.
Claims Integrate the Alleged Exception Into a Practical Application
The present claims define a specific monitoring method for a particular type of cancer (hepatocellular carcinoma), including specific extracellular vesicle (EV) isolation and EV lysing steps, which represent physical transformations of the sample. Further, Applicant respectfully submits that the EVs are a specialized subcellular structure, and isolating and lysing them and then analyzing the lysed mixture are not "routine laboratory practices" as is suggested in the Office Action. Additionally, the isolating, lysing, and ELISA-based measuring steps, which make up a large portion of the method, cannot be carried out in the human mind. For example, the ELISA-based measurement step requires a specific monoclonal antibody defined by VH/VL sequence identity, which further ties the claim to a specific, practical application.
Specifically, as demonstrated in the specification, the present method improves diagnostic sensitivity and specificity for monitoring for a specific cancer, HCC. See, e.g., Application as filed, page 60.
The Claims Recite Significantly More
First, the claim method recites a non-conventional use of an EV-specific biomarker-specifically, NID1 within isolated and lysed EVs, not just within the sample generally.
Second, as mentioned above, the claimed method recites an ELISA-based measuring step that utilizes a monoclonal antibody defined by specific sequences, and thus is not a generic or conventional measurement step.
Third even if the individual steps of claim were considered conventional in certain respects (which Applicant refutes), the combination and order of these steps (i.e., EV isolation and lysing, ELISA-based measuring with monoclonal antibody and, optionally, additional threshold-based determinations [claims 7 and 8]) cannot fairly be considered as "routine" in total.
Examiner’s Response:
Applicant states, “The present claims define a specific monitoring method for a particular type of cancer (hepatocellular carcinoma), including specific extracellular vesicle (EV) isolation and EV lysing steps, which represent physical transformations of the sample. Further, Applicant respectfully submits that the EVs are a specialized subcellular structure, and isolating and lysing them and then analyzing the lysed mixture are not "routine laboratory practices" as is suggested in the Office Action. Additionally, the isolating, lysing, and ELISA-based measuring steps, which make up a large portion of the method, cannot be carried out in the human mind. For example, the ELISA-based measurement step requires a specific monoclonal antibody defined by VH/VL sequence identity, which further ties the claim to a specific, practical application.”
MPEP 2106.05(g) Insignificant Extra-Solution Activity
(3) Whether the limitation amounts to necessary data gathering and outputting, (i.e., all uses of the recited judicial exception require such data gathering or data output). See Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015) (presenting offers and gathering statistics amounted to mere data gathering). This is considered in Step 2A Prong Two and Step 2B.
Examples of activities that the court have found to be insignificant extra-solution activity:
Mere Data Gathering
Vi. Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis).
MPEP 2106.05(d) Well-Understood, Routine, Conventional Activity
II. The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity:
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
Step 2A Is a Two-Prong Inquiry
Prong One whether a claim recites a judicial exception, and if so, then determine in Prong Two if the recited judicial exception is integrated into a practical application of that exception. Together, these prongs represent the first part of the Alice/Mayo test, which determines whether a claim is directed to a judicial exception.
2106.04(b) states: The courts have identified the following concepts and products as examples of laws of nature or natural phenomena:
v. a correlation between the presence of myeloperoxidase in a bodily sample (such as blood or plasma) and cardiovascular disease risk, Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017)
Thus, in a claimed method of treating cancer with chemotherapy, the cancer cells’ inability to survive chemotherapy is not considered to be a law of nature. Similarly, in a claimed method of treating headaches with aspirin, the human body’s natural response to aspirin is not considered to be a law of nature. These claims are accordingly eligible at Prong One unless they recite another exception, in which case they require further analysis in Prong Two (and Step 2B, if needed) to determine their eligibility.
Claim 1 is directed to routine laboratory procedures
Collecting a sample from the subject
Centrifuging the sample
Isolating extracellular vesicles (EV) from the serum, optionally via centrifuge and/or purification
Lysing EV
Measuring NID1
Comparing measured NID1, to NID1 levels in controls without HCC
Diagnosing the subject with increased risk HCC if NID1 measured amount exceeds NID1 levels in controls without HCC
NID1 measured by ELISA using antibody comprising 90% sequence identity with SEQ ID NOs: 41 and 42
2106.04(d)(2) Particular Treatment and Prophylaxis in Step 2A Prong Two
A claim reciting a judicial exception is not directed to the judicial exception if it also recites additional element(s) demonstrating that the claim as a whole integrates the exception into a practical application. One way to demonstrate such integration is when the additional elements apply or use the recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. The application or use of the judicial exception in this manner meaningfully limits the claim by going beyond generally linking the use of the judicial exception to a particular technological environment, and thus transforms a claim into patent-eligible subject matter. Such claims are eligible at Step 2A, because they are not "directed to" the recited judicial exception.
Applicant states that the Claims Recite Significantly More, First, the claim method recites a non-conventional use of an EV-specific biomarker-specifically, Second the claimed method recites an ELISA-based measuring step that utilizes a monoclonal antibody defined by specific sequences, Third the combination and order of these steps (i.e., EV isolation and lysing, ELISA-based measuring with monoclonal antibody and, optionally, additional threshold-based determinations [claims 7 and 8]) cannot fairly be considered as "routine" in total.
The use of a non-conventional EV-specific biomarker-specifically, NID1 within isolated and lysed EVs
ELISA-based measuring step that utilizes a monoclonal antibody
The combination and order of these steps (i.e., EV isolation and lysing, ELISA-based measuring with monoclonal antibody
MPEP 216.04(d)(2)
The application or use of the judicial exception in this manner meaningfully limits the claim by going beyond generally linking the use of the judicial exception to a particular technological environment, and thus transforms a claim into patent-eligible subject matter. Such claims are eligible at Step 2A, because they are not "directed to" the recited judicial exception.
Applicant states, “an ELISA-based measuring step that utilizes a monoclonal antibody defined by specific sequences”.
MPEP 2106.04(d)(2) Particular Treatment and Prophylaxis in Step 2A Prong Two
The particular treatment or prophylaxis consideration originated as part of the other meaningful limitations consideration discussed in MPEP § 2106.05(e) and shares the same legal basis in Supreme Court jurisprudence as that consideration. However, recent jurisprudence has provided additional guidance that is especially relevant to only a subset of claims, thus warranting the elevation of the particular treatment or prophylaxis consideration to become a stand-alone consideration in the Step 2A Prong Two analysis. Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd., 887 F.3d 1117, 126 USPQ2d 1266 (Fed. Cir. 2018). The claims in Vanda recited a method of treating a patient having schizophrenia with iloperidone, a drug known to cause QTc prolongation (a disruption of the heart’s normal rhythm that can lead to serious health problems) in patients having a particular genotype associated with poor drug metabolism. 887 F.3d at 1121, 126 USPQ2d at 1269-70. In particular, the claims recited steps of: (1) performing a genotyping assay to determine if a patient has a genotype associated with poor drug metabolism; and (2) administering iloperidone to the patient in a dose range that depends on the patient’s genotype. Id. Although Vanda’s claims recited a law of nature (the naturally occurring relationship between the patient’s genotype and the risk of QTc prolongation) like the claims in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 101 USPQ2d 1961 (2012), the Federal Circuit distinguished them from the Mayo claims based on the differences in the administration steps. In particular, the court explained that Mayo’s step of administering a drug to a patient was performed in order to gather data about the recited laws of nature, and this step was thus ancillary to the overall diagnostic focus of the claims. 887 F.3d at 1134-35, 126 USPQ2d at 1280. In contrast, Vanda’s claims used the recited law of nature to more safely treat the patients with the drug, thereby reducing the patient’s risk of QTc prolongation. 887 F.3d at 1135, 126 USPQ2d at 1280. Accordingly, the court held Vanda’s claims eligible at the first part of the Alice/Mayo test (Step 2A) because the claims were not "directed to" the recited judicial exception. 887 F.3d at 1136, 126 USPQ2d at 1281.
Examiner interprets the use of a specific sequence of monoclonal antibody as ancillary to the overall diagnostic focus of the claims and was used to gather data about the recited laws of nature. Claim 1 concludes with “diagnosing the subject with an increased risk of HCC if the measured amount of NID1 in the lysed mixture exceeds the amount of NID1 reflective of control subjects without HCC”, this step is a mental process.
2106.04(a) Abstract Ideas
To facilitate examination, the Office has set forth an approach to identifying abstract ideas that distills the relevant case law into enumerated groupings of abstract ideas.
The enumerated groupings of abstract ideas are defined as:
3) Mental processes – concepts performed in the human mind (including an observation, evaluation, judgment, opinion) (see MPEP § 2106.04(a)(2), subsection III).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-17 and 19-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 9, and 17 are drawn to an antibody that binds NID1, wherein said antibody comprises a VH having at least 90% sequence identity with SEQ ID NO: 41 and a VL having at least 90% sequence identity with SEQ ID NO: 42. The claims encompass a large number of anti-NID1 antibodies having diverse heavy and light chain CDR amino acid sequences. Following a review of the specification, it appears that Applicant has disclosed one anti-NID1 antibody, specifically, an anti-NID1 antibody that comprises the VH of SEQ ID NO: 41 and the VL of SEQ ID NO: 42; however in view of this disclosure, Applicant is claiming a broad genus of molecules that would be expected to encompass multiple anti-NID1 antibodies having diverse heavy and light chain CDR sequences. Even though Applicant has disclosed one species within said genus, the specification does not provide adequate written description for the entire claimed genus, because one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genus claimed, specifically, which light and heavy chain CDR sequences (and combinations of said CDR sequences) give rise to antibody molecules capable of binding NID1. As detailed below Applicant’s disclosure is not sufficient to demonstrate possession of the entire claimed genus, and as such Applicant’s disclosure does not satisfy the written description requirement of 35 U.S.C. 112(a).
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proceedings of the National Academy of Sciences, 1982, 79:1979-1983). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function.
MacCallum et al. (Journal of Molecular Biology, 1996, 262:732-745) analyzed many different antibodies for interactions with antigen and state that although CDR3 of the heavy and light chain dominates, a number of residues outside the standard CDR definitions make antigen contacts (see page 733, right column) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left column).
The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site is underscored by Casset et al. (Biochemical and Biophysical Research Communications, 2003, 307:198-205), which constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (see entire document). Casset et al. also states that although CDR H3 is at the center of most if not all antigen interactions, other CDRs play an important role in the recognition process (page 199, left column) and this is demonstrated in this work by using all CDRs except CDR L2 and additionally using a framework residue located just before the CDR H3 (see page 202, left column). Holm et al. (Molecular Immunology, 2007:1075-1084) describes the mapping of an anti-cytokeratin antibody and found that in addition to the involvement of the residues in the CDR3 of the heavy chain in antigen binding, a residue in CDR2 of the light chain was also involved (abstract). Chen et al. (Journal of Molecular Biology, 1999, 293:865-881) describe high affinity variant antibodies binding to VEGF wherein the results show that the antigen binding site is almost entirely composed of residues from heavy chain CDRs, CDR-H1, H2, H3 (page 866). There is insufficient evidence or nexus that would lead the skilled artisan to predict the ability of an antibody to bind to NID1 comprising fewer than 6 complete CDR regions of an antibody known to bind NID1.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the instant case, Applicant has disclosed one species within the genus claimed; however given the substantial antibody structure variation within the genus, as well as the high level of unpredictability in the art, the disclosure of one species comprised within the claimed genus is not sufficiently representative of the entire genus.
Furthermore Applicant has not disclosed relevant, identifying characteristics of CDR region amino acid sequences (or combinations thereof) that confer upon an antibody the ability to bind NID1. Absent a description of the at least minimal structural features correlating with a functional ability to bind NID1 which are shared by members of a genus commonly sharing this function, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish which heavy and light chain CDR amino acid sequences (or combinations thereof) may be combined such that the resultant heavy and light chain variable regions comprise six CDRs that confer the ability to bind NID1.
Although screening techniques can be used to isolate antibodies that possess the ability to bind NID1, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. v. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, “The purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must also convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.”
Claims 19 and 20 are included in this rejection, because the claim allows for anti-NID1 antibodies having variability within the heavy and light chain CDRs. Absent empirical determination one skilled in the art would be unable to readily determine which variants of the recited CDRs should be comprised within an antigen-binding site, such that said antigen-binding site is capable of binding NID1.
Accordingly given the unpredictability associated with antibody CDR region changes on antigen binding and given the lack of particularity with which the claimed antibodies are described in the specification, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish at least most of the members of the genus to which the claims are directed, and therefore the specification would not reasonably convey to the skilled artisan that Applicant was in possession of the claimed invention at the time the application was filed.
Applicant’s Arguments:
Applicant respectfully disagrees.
While Applicant respectfully disagrees with the rejection, in an effort solely to expedite prosecution, the claims have been amended to recite 90% sequence identity to various sequences recited in the claims. Applicant respectfully submits that the present amendment narrows the claimed genus, and based on the specific antibodies and binding epitopes disclosed in the specification, a person of ordinary skill in the art would reasonably conclude that the inventors had possession of the presently claimed invention at the time of filing.
Examiner’s Response:
Applicant states, “the claims have been amended to recite 90% sequence identity to various sequences recited in the claims. Applicant respectfully submits that the present amendment narrows the claimed genus, and based on the specific antibodies and binding epitopes disclosed in the specification, a person of ordinary skill in the art would reasonably conclude that the inventors had possession of the presently claimed invention at the time of filing.”
MPEP 2163. II.A.3.ii
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.). Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. For example, in the molecular biology arts, if an applicant disclosed an amino acid sequence, it would be unnecessary to provide an explicit disclosure of nucleic acid sequences that encoded the amino acid sequence. Since the genetic code is widely known, a disclosure of an amino acid sequence would provide sufficient information such that one would accept that an inventor was in possession of the full genus of nucleic acids encoding a given amino acid sequence, but not necessarily any particular species. Cf. In re Bell, 991 F.2d 781, 785, 26 USPQ2d 1529, 1532 (Fed. Cir. 1993) and In re Baird, 16 F.3d 380, 382, 29 USPQ2d 1550, 1552 (Fed. Cir. 1994). If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph.
For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.). Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. For example, in the molecular biology arts, if an applicant disclosed an amino acid sequence, it would be unnecessary to provide an explicit disclosure of nucleic acid sequences that encoded the amino acid sequence. Since the genetic code is widely known, a disclosure of an amino acid sequence would provide sufficient information such that one would accept that an inventor was in possession of the full genus of nucleic acids encoding a given amino acid sequence, but not necessarily any particular species. Cf. In re Bell, 991 F.2d 781, 785, 26 USPQ2d 1529, 1532 (Fed. Cir. 1993) and In re Baird, 16 F.3d 380, 382, 29 USPQ2d 1550, 1552 (Fed. Cir. 1994). If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph.
In the instant case, Applicant has disclosed one species within the genus claimed, an antibody that binds NID1 comprising SEQ ID NOs: 41 and 42; however given the substantial antibody structure variation within the genus, as well as the high level of unpredictability in the art, the disclosure of one species comprised within the claimed genus is not sufficiently representative of the entire genus antibodies that bind NID1 comprising 90% sequence identity with the sequences SEQ ID NOs: 41 and 42.
Conclusion
Claim 18 is objected to.
Claims 1-17, and 19-22 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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